Machado-Joseph disease (MJD) is a neurodegenerative disorder with auto-soma1 dominant inheritance. We have carried out electrophysiological studies in 8 individuals belonging to a Danish family with several affected members. Five had an expanded trinucleotide (CAG) repeat sequence in the MJDl gene on chromosome 14 indicating MJD, while 3 unaffected individuals had normal repeat lengths. Three individuals with repeat expansion had clinical symptoms and signs of the Machado or "type 111" phenotype, whereas 2 had slight symptoms and signs only. Electrophysiological evaluation included visual, somatosensory, and auditory brain stem evoked potentials, quantitative electromyography, and nerve conduction studies. In the patients with clinical MJD, evoked potential studies showed multimodal abnormalities, electromyography showed neurogenic changes, and nerve conduction studies showed signs of severe loss of motor and sensory nerve fibers. Of the 2 patients with slight symptoms and signs, 1 had evidence of peripheral and central affection, while the other had slight signs of a central affection. This study provides insight into the distribution and character of electrophysiological abnormalities in MJD of putative importance for an understanding of the pathogenesis of the disease, and for monitoring disease progress, or the outcome of a possible treatment. 0